Alcohol and Alcoholism Advance Access originally published online on February 5, 2009
Alcohol and Alcoholism 2009 44(3):267-271; doi:10.1093/alcalc/agp005
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Activation of Liver Tryptophan Pyrrolase Mediates the Decrease in Tryptophan Availability to the Brain after Acute Alcohol Consumption by Normal Subjects
1 Cardiff School of Health Sciences, University of Wales Institute Cardiff (UWIC), Western Avenue, Cardiff CF5 2YB, Wales, UK
2 Department of Psychiatry, Neurobehavioral Research Laboratory and Clinic, School of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
* Corresponding author: Cardiff School of Health Sciences, University of Wales Institute Cardiff (UWIC), Western Avenue, Cardiff CF5 2YB, Wales, UK. Tel: +44-29-2041-6858; Fax: +44-29-2041-6982; E-mail: ABadawy{at}uwic.ac.uk
Received 28 November 2008; first review notified 23 December 2008; in revised form 5 January 2009; accepted 15 January 2009; advance access publication 5 February 2009
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Abstract |
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Aims: We have previously suggested that acute ethanol consumption by normal subjects decreases the availability of circulating tryptophan (Trp) to the brain by activating liver Trp pyrrolase, the first and rate-limiting enzyme of the (major) kynurenine pathway of Trp degradation. The aim of the present study was to examine this hypothesis further by measuring plasma levels of kynurenine metabolites following alcohol consumption. Methods: After an overnight fast and a light breakfast, each of 10 healthy subjects received one of five drinks (placebo and doses of ethanol of 0.2, 0.4, 0.6 and 0.8 g/kg body weight in tonic water) on five different occasions. Blood samples were withdrawn 2 h later and plasma was analysed for concentrations Trp, competing amino acids (CAA) and kynurenine metabolites. Results: Along with the depletion of plasma Trp and the decrease in its availability to the brain, as expressed by the ratio of [Trp]/[CAA], plasma kynurenine was elevated by doses of ethanol of 0.2–0.8 g/kg body weight. The ratio% of [kynurenine]/[Trp], an index of the expression of Trp pyrrolase activity, was also increased by all doses of ethanol. Conclusions: We conclude that activation of liver Trp pyrrolase mediates the depletion of plasma Trp and the decrease in its availability to the brain induced by acute ethanol consumption.